Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In female rats aspirin-induced gastrin mucosal damage was increased and glycoprotein synthesis decreased by fasting and by insulin administration. Glucose added to the drinking water during the fasting period reduced mucosal damage and increased glycoprotein synthesis to control levels. Alloxan diabetes did not affect mucosal damage or glycoprotein synthesis. Alloxan diabetes plus insulin restored blood glucose levels to normal, and susceptibility to aspirin damage and glycoprotein synthesis were also normal. Alloxan diabetes plus fasting restored blood glucose levels to normal but increased aspirin-induced mucosal damage and reduced glycoprotein synthesis. In vitro incubation of gastric mucosal homogenates showed that diburyryl cyclic AMP and theophylline inhibited glycoprotein synthesis but dibutyryl cyclic GMP had no significant effects. The importance of an adequate supply of glucose to the gastric mucosa and the effects of cyclic nucleotides on glycoprotein synthesis are discussed.
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PMID:Effects of blood glucose levels on aspirin-induced gastric mucosal damage. 20 Jan 38

The effect of proglumide ((+/-)-4-benzamido-N,N-dipropyl-glutaramic acid), a gastrin and cholecystokinin receptor antagonist, has been studied on the fasting plasma glucose (FPG) and insulin levels in normal and alloxan-diabetic mice. In normal mice, proglumide, administered as a single oral dose or twice daily for five consecutive days, did not produce any alteration in those parameters. Injection of alloxan monohydrate (70 mg kg-1 i.v.) produced a significant decrease in plasma insulin and a significant elevation of FPG levels on the 5th day after its administration as evidence of diabetes mellitus. Proglumide sodium, given as a single acute dose on the 5th day of alloxan injection, or as a twice daily dose for 5 days immediately after alloxan injection, significantly exacerbated the hyperglycaemia and further decreased the plasma insulin levels thus worsening the diabetogenic effect of alloxan. These observations point to a possible involvement of cholecystokinin (CCK) in alloxan-induced diabetes and indicate a need for monitoring the levels of FPG in diabetic patients being treated with a high dose of proglumide or other CCK-antagonists.
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PMID:Proglumide, a cholecystokinin receptor antagonist, exacerbates alloxan-induced diabetes mellitus in Swiss mice. 289 31

Beta cell replacement and regeneration therapies seem promising approaches to the treatment of insulin-dependent diabetes. The short supply in beta cells from cadaveric organ donors and the very low replication capacity of human beta cells have spurred efforts to find robust ways of (re-)generating beta cells in vitro and in vivo. In the pancreas, both the capacity of regeneration and the mechanism involved can differ significantly depending on the experimental model, as it has also been found in other organs like the liver. Robust expansion of the beta cell mass in adult rodent pancreas doesn't normally occur after partial (50-70%) pancreatectomy nor after beta cell destruction by streptozotocin or alloxan. However, extensive tissue injury and treatment with certain gastrointestinal hormones, like gastrin and growth factors from the EGF-family can stimulate beta cell regeneration. Whereas a slow rate of beta cell mass expansion can result from beta cell replication, more robust regeneration depends largely on neogenesis from precursor cells. Precursor cells can be derived from stem cells or from pancreatic exocrine cells which are known to retain phenotypic plasticity and can transdifferentiate into, amongst others, endocrine cells. Identifying the conditions involved in the regulation of cellular plasticity and regenerative growth may lead to new pharmacological strategies for the treatment of diabetes.
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PMID:Beta cell regeneration. 1822 Jun 12

A longstanding unsettled question is whether pancreatic beta cells originate from exocrine duct cells. We have now used genetic labeling to fate map embryonic and adult pancreatic duct cells. We show that Hnf1beta+ cells of the trunk compartment of the early branching pancreas are precursors of acinar, duct, and endocrine lineages. Hnf1beta+ cells subsequent form the embryonic duct epithelium, which gives rise to both ductal and endocrine lineages, but not to acinar cells. By the end of gestation, the fate of Hnf1beta+ duct cells is further restrained. We provide compelling evidence that the ductal epithelium does not make a significant contribution to acinar or endocrine cells during neonatal growth, during a 6 month observation period, or during beta cell growth triggered by ligation of the pancreatic duct or by cell-specific ablation with alloxan followed by EGF/gastrin treatment. Thus, once the ductal epithelium differentiates it has a restricted plasticity, even under regenerative settings.
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PMID:Pancreatic exocrine duct cells give rise to insulin-producing beta cells during embryogenesis but not after birth. 2005 54

One week of treatment with EGF and gastrin (EGF/G) was shown to restore normoglycemia and to induce islet regeneration in mice treated with the diabetogenic agent alloxan. The mechanisms underlying this regeneration are not fully understood. We performed genetic lineage tracing experiments to evaluate the contribution of beta cell neogenesis in this model. One day after alloxan administration, mice received EGF/G treatment for one week. The treatment could not prevent the initial alloxan-induced beta cell mass destruction, however it did reverse glycemia to control levels within one day, suggesting improved peripheral glucose uptake. In vitro experiments with C2C12 cell line showed that EGF could stimulate glucose uptake with an efficacy comparable to that of insulin. Subsequently, EGF/G treatment stimulated a 3-fold increase in beta cell mass, which was partially driven by neogenesis and beta cell proliferation as assessed by beta cell lineage tracing and BrdU-labeling experiments, respectively. Acinar cell lineage tracing failed to show an important contribution of acinar cells to the newly formed beta cells. No appearance of transitional cells co-expressing insulin and glucagon, a hallmark for alpha-to-beta cell conversion, was found, suggesting that alpha cells did not significantly contribute to the regeneration. An important fraction of the beta cells significantly lost insulin positivity after alloxan administration, which was restored to normal after one week of EGF/G treatment. Alloxan-only mice showed more pronounced beta cell neogenesis and proliferation, even though beta cell mass remained significantly depleted, suggesting ongoing beta cell death in that group. After one week, macrophage infiltration was significantly reduced in EGF/G-treated group compared to the alloxan-only group. Our results suggest that EGF/G-induced beta cell regeneration in alloxan-diabetic mice is driven by beta cell neogenesis, proliferation and recovery of insulin. The glucose-lowering effect of the treatment might play an important role in the regeneration process.
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PMID:Beta Cell Mass Restoration in Alloxan-Diabetic Mice Treated with EGF and Gastrin. 2645 42